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Singh V, Moran JC, Itoh Y, Soto IC, Fontanesi F, Couvillion M, Huynen MA, Churchman LS, Barrientos A, Amunts A
Nat. Struct. Mol. Biol. 31 (12) 1838-1847 [2024-12-00; online 2024-08-12]
In mammalian mitochondria, mRNAs are cotranscriptionally stabilized by the protein factor LRPPRC (leucine-rich pentatricopeptide repeat-containing protein). Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-electron microscopy structure in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N terminus of mS31 through recognition of the LRPPRC helical repeats. Together, the proteins form a corridor for handoff of the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used RNA sequencing, metabolic labeling and mitoribosome profiling, which showed a transcript-specific influence on mRNA translation efficiency, with cytochrome c oxidase subunit 1 and 2 translation being the most affected. Our data suggest that LRPPRC-SLIRP acts in recruitment of mitochondrial mRNAs to modulate their translation. Collectively, the data define LRPPRC-SLIRP as a regulator of the mitochondrial gene expression system.
PubMed 39134711
DOI 10.1038/s41594-024-01365-9
Crossref 10.1038/s41594-024-01365-9
mid: NIHMS2030709
pmc: PMC11637978
pii: 10.1038/s41594-024-01365-9